Diisopropylethylamine → 2-(4-fluorophenyl)-N-methyl-5-(3-((2-(3-methyl-1,2,4-oxadiazol-5-yl)propan-2-yl)carbamoyl)phenyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridine-3-carboxamide

Participants

Reaction Steps

3-(2-(4-fluorophenyl)-3-(methylcarbamoyl)-6-((2,2,2-trifluoroethyl)amino)furo[2,3-b]pyridin-5-yl)benzoic acid (40 mg, 0.082 mmol) was taken up in DMF (1 ml) and treated with N-ethyl-N-isopropylpropan-2-amine (43 μL, 0.25 mmol), 2-(3-methyl-1,2,4-oxadiazol-5-yl)propan-2-amine hydrochloride (17 mg, 0.098 mmol) followed by 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (47 mg, 0.12 mmol). The reaction mixture was allowed to stir for 1 h then the reaction was quenched with MeOH (1 mL) and the crude mixture was purified via preparative LC/MS with the following conditions: Column:Waters XBridge C18, 19×200 mm, 5-μm particles; Guard Column:Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: water with 20-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 20-mM ammonium acetate; Gradient: 50-90% B over 40 minutes, then a 4-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the product was 17.0 mg, and its estimated purity by LCMS analysis was 96%. Two analytical LC/MS injections were used to determine the final purity. Injection 1 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 1 mL/min. retention time: 2.95 min; M+H: 611. Injection 2 conditions: Column:Waters BEH C18, 2.0×50 mm, 1.7-μm particles; Mobile Phase A: 5:95 methanol:water with 10 mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10 mM ammonium acetate; Temperature: 40° C.; Gradient: 0.5 min hold at 0% B, 0-100% B over 4 minutes, then a 0.5-minute hold at 100% B; Flow: 0.5 mL/min. retention time: 3.89 min; M+H: 611. Proton NMR was acquired in deuterated DMSO. 1H NMR (500 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.41-8.33 (m, 1H), 8.01-7.88 (m, 4H), 7.68 (s, 1H), 7.65-7.57 (m, 2H), 7.34 (t, J=8.7 Hz, 2H), 6.62 (t, J=6.3 Hz, 1H), 4.24-4.09 (m, 2H), 2.79 (d, J=4.6 Hz, 3H), 2.31 (s, 3H), 1.70 (s, 6H.

Provenance & Evidence